This research program will be focused primarily on the serum lipoproteins, with the underlying assumption that they are important biochemical entities having significant relationships to atherosclerosis and other lipid disorders. The elucidation of their chemical, structural, and metabolic properties is expected to provide insights into the physiological and biochemical mechanisms of those relationships. Knowledge of lipoprotein distributions in individuals is highly significant clinical information. Our investigations of the lipoproteins will address a variety of problems and employ a broad scope of experimental techniques and skills. The principal tools that we expect to use, develop, and seek new applications for include: ultracentrifugation, electrophoresis, electron microscopy, fluorescence spectroscopy, chromatography, isotope tracing, enzymatic methods, and computers. Analytical and chemical studies will emphasize the development and application of methods for the analysis of lipoprotein distributions and lipids, and refinement of ultracentrifugal and electrophoretic procedures for the isolation, subfractionation and quantitative determination of lipoproteins. It is proposed to establish an automated rapid screening facility for quantitative electrophoretic lipoprotein determination in large numbers of blood samples for clinical atherosclerosis research. We will attempt to develop structural and functional concepts of lipoproteins and their distributions by studying properties of interaction products of their lipid and protein moieties, and the morphologies and properties of partially degraded and physically or enzymatically reassembled structures. Effects of perturbations on distribution of native structures and on related model lipid-protein complexes by physical and chemical agents will be investigated. Postulated models of lipoprotein structural organization will be evaluated in terms of these findings. Enzymatic processes involving lipoproteins will be studied to gain structural information and to relate them to biosynthesis, metabolic function, and their role in human diseases. In certain diseases of lipid dysfunction, lipoprotein abnormalities will be correlated with metabolic defects.